Bronchopulmonary dysplasia (BPD) is a major and costly cause of long-term pulmonary disability in extremely low birth weight (ELBW <1000 g and <30 weeks gestation) infants. The pathogensis of BPD is multi-factorial, has a genetic component, and involves lung injury and inflammation secondary to treatment with oxygen and mechanical ventilation in an underdeveloped, immature lung. Inhaled Nitric Oxide (iNO) therapy in ELBW infants increases survival without BPD, improves pulmonary outcome through 1 year of age, is cost effective, and is not associated with short- or long-term adverse effects. However 50% of iNO-treated infants still develop BPD. ELBW infants are developmentally deficient in pulmonary surfactant and receive replacement surfactant treatment at birth. We observed that deteriorations in respiratory status in ventilated infants are associated with dysfunctional surfactant and low content of surfactant proteins B and C, and propose that these episodes contribute to development of BPD by increasing lung inflammation and injury secondary to greater exposure to oxygen and ventilator-induced volutrauma. INO therapy transiently improves surfactant function, and normal surfactant function in treated infants is associated with improved outcome. We propose that the combination of iNO and late surfactant will interact to promote alveolar development and reduce continuing lung injury, respectively. We hypothesize that late doses of surfactant administered to infants receiving iNO and requiring mechanical ventilation at 7-14 d of age is safe and will increase survival without BPD at 36 wk post menstrual age (PMA). Aim 1 assesses the effect of late doses of surfactant on the occurrence and severity of BPD in ventilated ELBW infants who are receiving iNO in a multi-center randomized, blinded, controlled trial. Demonstrating an increase from 50 to 62.5% in the primary outcome of survival without BPD at 36 wk PMA requires 500 infants to have 80% power and a two-sided alpha of 0.05, allowing for one interim analysis, 7% multiple births, and stopping for either efficacy or futility. Secondary outcomes include discharge off respiratory support at 40 wk (term), duration of ventilation and hospitalization, and pulmonary morbidity and neurodevelopmental outcome at 1 and 2 years of age. Aim 2 assesses effects of late surfactant treatment on surfactant status and lung inflammatory biomarkers. Surfactant is isolated from serial tracheal aspirate samples to determine the association of in vitro surfactant properties with respiratory status, surfactant treatment, and outcome. Assays of tracheal aspirate cytokines will examine safety and potential anti- inflammatory effects of combined treatment. A DNA repository will be established for future analysis of polymorphisms associated with BPD and response to treatment. This application describes the Clinical Coordinating Center for the trial. Project Narrative Bronchopulmonary Dysplasia (BPD) is the chronic lung disease that occurs in premature infants and is associated with prolonged and costly hospitalization, long-term lung diseases, and neurodevelopmental abnormalities and mortality, with a prevalence estimated at 30,000 cases/year in the U.S. This clinical trial by experienced investigators utilizing an established trial network will determine the safety and efficacy of a new therapeutic approach for prevention of BPD in premature infants. This research has potential to decrease chronic infant lung disease and asthma, important areas of public health, reduce cost of care, and improve long-term outcome for premature infants.